Enhanced 3-Hydroxy-3-methyl-Glutaryl Coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor

Maria Gabriella Caruso, Maria Notarnicola, Mariarosaria Santillo, Aldo Cavallini, Alfredo Di Leo

Research output: Contribution to journalArticle

Abstract

Background: We have previously shown that 63.3% of colorectal cancer neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR. Materials and methods: the tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR activity was measured by radiochemical assay using 14C-HMG-CoA as substrate. Results: HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p = 0.02, Wilcoxon Rank sum test)]. Conclusions: the cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.

Original languageEnglish
Pages (from-to)451-454
Number of pages4
JournalAnticancer Research
Volume19
Issue number1 A
Publication statusPublished - 1999

Keywords

  • Colorectal carcinoma
  • HMG-CoA reductase
  • Low density lipoprotein receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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